A sensitive and robust method for the simultaneous determination of thirty-three legacy and emerging per- and polyfluoroalkyl substances in human plasma and serum.

Legacy and emerging per- and polyfluoroalkyl substances (PFAS) have attracted growing attention due to their potential adverse effects on humans. We developed a method to simultaneously determine thirty-three PFAS (legacy PFAS, precursors, and alternatives) in human plasma and serum using solid phase extraction coupled to ultra-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS). The method yielded good linearity (>0.995) and excellent limits of detection (LODs) (0.0005~0.012 ng mL-1 in plasma and 0.002~0.016 ng mL-1 in serum). The relative recoveries ranged from 80.1 to 116%, with intra- and inter-day precision less than 14.3%. The robustness of this method has been tested continuously for 10 months (coefficients of variation <14.9%). Our method was successfully applied to the PFAS analysis of 42 real human plasma and serum samples collected from women. The proposed method is attractive for the biomonitoring of multi-class PFAS in human health risk assessment and epidemiological studies.

Associations between urinary monohydroxylated polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion and health risk assessment in a large case-control study in China.

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 µg/g Creatinine) was higher than that in the case group (14.2 µg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10-6). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age.

Environmental Exposure to 6:2 Polyfluoroalkyl Phosphate Diester and Impaired Testicular Function in Men.

6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) has been demonstrated to disrupt reproductive endocrine functions using experimental studies. However, evidence from humans is not available yet. This cross-sectional study aims to assess the relationship between 6:2 diPAP exposure and the testicular function among adult men. A total of 902 men seeking preconception care were included. Plasma 6:2 diPAP concentrations were determined, while the testicular function was assessed via semen quality and reproductive hormones in serum. The association was assessed by multiple linear regression. Stratified analyses by age and body mass index (BMI) were conducted to assess the potential effect modification by these two variables. Regression analyses revealed that 6:2 diPAP exposure was significantly inversely associated with androgens [i.e., total testosterone (TT) and free androgen index (FAI)], markers of testosterone production potential [i.e., TT/luteinizing hormone (LH) and FAI/LH], estradiol, and insulin-like factor 3, a biomarker of Leydig cell function. These associations were robust in sensitivity analyses. However, age and BMI did not modify these associations, and no association was observed between 6:2 diPAP and semen quality. Our study suggests that exposure to 6:2 diPAP may inhibit androgen synthesis and impair Leydig cell function in adult men.

Association of emerging and legacy per- and polyfluoroalkyl substances with unexplained recurrent spontaneous abortion.

Emerging per- and polyfluoroalkyl substances (PFAS) alternatives are increasingly used in daily life. Although legacy PFAS have been associated with miscarriage in previous studies, it remains unknown whether exposure to emerging and legacy PFAS has any impact on the risk of unexplained recurrent spontaneous abortion (URSA). We conducted a case-control study with 464 URSA cases who had at least 2 unexplained miscarriages and 440 normal controls who had at least one normal livebirth. Concentrations of 21 PFAS in plasma, including three emerging PFAS alternatives, eight linear and branched PFAS isomers, four short-chain PFAS, and six legacy PFAS, were measured by ultra-performance liquid chromatography coupled with a tandem mass spectrometry (UPLC-MS/MS). Multiple logistic regression was applied to evaluate the relationship between PFAS and URSA risk. Perfluorooctanoic acid (PFOA, median: 6.18 ng/mL), perfluorooctane sulfonate (PFOS, median: 4.10 ng/mL), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA, median: 2.27 ng/mL) were the predominant PFAS in the controls. Exposure to 6:2 Cl-PFESA [adjusted odds ratio (aOR) = 1.18 (95% CI: 1.00, 1.39)] and hexafluoropropylene oxide dimer acid (HFPO-DA) [aOR = 1.35 (95% CI: 1.15, 1.59)] were significantly associated with increased risks of URSA. Women with older age (>30 years old) had a stronger association between PFAS and URSA. Our results suggest that emerging PFAS alternatives may be an important risk factor for URSA.

Association between Prenatal Exposure to PFAS and Fetal Sex Hormones: Are the Short-Chain PFAS Safer?

Epidemiologic evidence regarding the effects of in utero exposure to per- and polyfluoroalkyl substances (PFAS), particularly short-chain PFAS, on fetal reproductive hormones is limited and inconsistent. This study aimed to assess the relationship between maternal PFAS exposure and fetal reproductive hormones. A total of 752 mother-infant pairs who were recruited in the Shanghai Birth Cohort Study between 2013 and 2016 were selected. We quantified 10 PFAS, including two short-chain PFAS congeners (perfluorobutanesulfonate, PFBS and perfluoroheptanoic acid, PFHpA), in maternal blood plasma in early pregnancy. Dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone (TT) were measured in the umbilical cord blood using chemiluminescence kits. Free androgen index (FAI) was calculated by TT divided by SHBG. Multiple linear regression found that one ln-unit increase in maternal PFBS was associated with decreases in FSH (-0.159; 95% CI: -0.290, -0.029), LH (-0.113; 95% CI: -0.221, -0.004), and FAI (-0.009; 95% CI: -0.017, -0.001). In addition, PFHpA showed negative associations with LH (-0.154; 95% CI: -0.297, -0.011) and FAI (-0.008; 95% CI: -0.014, -0.002). When PFAS were analyzed in quartiles, significant negative associations were observed between PFBS and FSH, and between PFHpA and FAI. Overall, prenatal exposure to PFBS and PFHpA was associated with the disturbance of fetal gonadotropins as well as free androgen level in this prospective cohort, suggesting that the reproductive toxicity of short-chain PFAS may not be neglected.

[Mesenchymal stem cells for the treatment of male infertility].

Mesenchymal stem cells (MSC), as a type of multifunction cells capable of self-renewal and multi-directional differentiation and with a low immunogenicity, have been widely applied in life sciences and medicine in recent years. Male infertility is very complicated pathogenically and there is no ideal method for its treatment. The potential ability of multi-differentiation and paracrine function of MSCs is bringing new hope to patients with male infertility. MSCs can be derived from the bone marrow, adipose tissue, and umbilical cord, on which lots of studies, either in vitro or in vivo, have been conducted and achieved satisfactory results. Many findings indicate that MSCs can differentiate into germ-like cells if specifically induced or transplanted into the testis, improve the local microenvironment of spermatogenesis and reconstruct the spermatogenic process by secreting nutritional factors after transplantation. This article presents an overview of the advances in the studies and application prospects of MSCs in male infertility.

Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China.

Exposure to chemicals may affect liver enzyme to increase the risk of liver diseases. Perfluoroalkyl acids (PFAAs) are one kind of persistent organic pollutants with hepatotoxic effect in organism. However, data is scarce to characterize the hepatotoxic effects of specific structural PFAA isomers in general population. To address this data gap, we evaluated the association between serum PFAAs concentration and liver function biomarkers in the Isomers of C8 Health Project in China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure 18 serum PFAAs, except for linear and branched isomers of PFOA/PFOS, nine perfluorinated carboxylic acids (PFCAs) and two perfluorinated sulfonic acids (PFSAs) were also included, in 1605 adult residents of Shenyang, China. Values for nine serum liver function biomarkers were determined by full-automatic blood biochemical analyzer. Linear regression was used to evaluate associations between PFAAs and continuous liver function biomarkers and logistic regression to assess markers dichotomized per clinical reference intervals. Results indicated that serum PFAAs concentrations were associated with liver biomarker levels suggestive of hepatotoxicity, especially for liver cell injury. For example, a 1 ln-unit increase in total- perfluorooctanoic acid (PFOA) exposure was associated with a 7.4% [95% confidence interval (CI): 3.9%, 11.0%] higher alanine aminotransferase (ALT) level in serum. Interestingly, we observed association between branched PFAA isomers and liver biomarkers. For example, one ln-unit increase in branched perfluorooctane sulfonate (PFOS) isomers exposure was associated with a 4.3% increase in ALT level (95% CI: 1.2%, 7.4%) and a 33.0% increased odds of having abnormal ALT (95% CI: 5.0%, 67.0%). Also, we found that PFNA had positive association with ALT [(6.2%, 95% CI: 3.1%, 9.4%) and AST levels (2.5%, 95% CI: 0.5%, 4.5%)]. Logistic regression results showed that PFPeA, PFHxA, PFNA, PFDoDA, PFTrDA and PFTeDA had statistically association with abnormal prealbumin. Conclusively, our results support previous studies showing association between PFAAs exposure and liver function biomarkers. We found new evidence that branched PFAAs isomer exposure is associated with the risk of clinically relevant hepatocellular dysfunction.

Overweight modifies the association between long-term ambient air pollution and prehypertension in Chinese adults: the 33 Communities Chinese Health Study.

BACKGROUND: Research regarding the interaction of ambient air pollution and overweight on prehypertension is scarce. We aimed to test whether overweight modifies the association between long-term exposure to ambient air pollution and prehypertension in Chinese adults. METHODS: A total of 16,188 Chinese adults, aged 18-74 years old, from 33 communities in 3 Northeastern Chinese cities were evaluated. Three-year average levels of particles with an aerodynamic diameter ≤ 10 µm (PM10), sulfur dioxides (SO2), nitrogen dioxides (NO2), and ozone (O3) were calculated at monitoring stations. Generalized additive models and 2-level regression analyses were applied. RESULTS: We observed significant interactions between air pollutants and overweight on prehypertension and blood pressure. The associations of PM10, SO2, NO2, and O3 with prehypertension were significant among overweight participants (Prevalence Rate Ratios (PRRs) per interquartile range (IQR) of air pollutants: 1.14-1.20), but not among normal weight participants (PRRs: 0.98-1.04). PM10, SO2, and O3 were significantly associated with systolic blood pressure (SBP), and the magnitudes of these associations were higher among overweight adults (increases in SBP per IQR of air pollutants: 1.82-4.53 mmHg) than those among normal weight adults (increases in SBP: 0.42-0.61 mmHg). For diastolic blood pressure (DBP), significant associations were mainly observed in overweight participants (increases in DBP: 0.80-1.63 mmHg). Further stratified analyses showed that all these interactions were stronger in women, the older, and participants living in areas with lower income levels or higher population density. CONCLUSIONS: Being overweight may enhance the effects of ambient air pollution on prehypertension and blood pressure in Chinese adults.

Association of perfluoroalkyl substances exposure with impaired lung function in children.

Previous studies have demonstrated associations between serum levels of perfluoroalkyl substances (PFASs) and asthma or asthma related-biomarkers. However, no studies have reported a possible relationship between PFASs exposure and lung function among children. The objective of the present study is to test the association between PFASs exposure and lung function in children from a high exposure area by using a cross-sectional case-control study, which included 132 asthmatic children and 168 non-asthmatic controls recruited from 2009 to 2010 in the Genetic and Biomarkers study for Childhood Asthma. Structured questionnaires were administered face-to-face. Lung function was measured by spirometry. Linear regression models were used to examine the influence of PFASs on lung function. The results showed that asthmatics in our study had significantly higher serum PFAS concentrations than healthy controls. Logistic regression models showed a positive association between PFASs and asthma, with adjusted odds ratios (ORs) ranging from 0.99 (95% confidence interval [CI]: 0.80-1.21) to 2.76 (95% CI: 1.82-4.17). Linear regression modeling showed serum PFASs levels were significantly negatively associated with three pulmonary function measurements (forced vital capacity: FVC; forced expiratory volume in 1s: FEV1; forced expiratory flow 25-75%: FEF25-75) among children with asthma, the adjusted coefficients between lung function and PFASs exposure ranged from -0.055 (95%CI: -0.100 to -0.010) for FVC and perfluorooctane sulfonate (PFOS) to -0.223 (95%CI: -0.400 to -0.045) for FEF25-75 and perfluorooctanoic acid (PFOA). PFASs were not, however, significantly associated with pulmonary function among children without asthma. In conclusion, this study suggests that serum PFASs are associated with decreased lung function among children with asthma.

Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.

Preparation of HMn2O4 lithium-ion sieves with low manganese dissolution loss for improved cycling stability.

Manganese-based lithium-ion sieves have become some of the promising adsorbents for extracting Li+ from brines. However, manganese dissolution loss (MDL) severely impairs the stability and cyclicity of ion sieves. A novel ozone eluent was first developed to extract Li+ from lithium manganese oxides, which decreased MDL decreased from 5.89% to 0.11%, and after ten regeneration cycles, the adsorption capacity retained 85.39% of the initial value, which was better than 55.15% when only hydrochloric acid (HCl) was used as the eluent. Based on these phenomena, the mechanism for the O3 lowering of MDL was investigated. First, the catalytic decomposition reaction of O3 competed with the disproportionation reaction, and the involvement of O3 inhibited the occurrence of the disproportionation reaction. Additionally, the presence of O3 and reactive oxygen species provided a preferential electron acceptor compared to Mn3+ during the migration of electrons from the bulk phase to the surface. In this study, MDL was greatly reduced with a very simple strategy, and the cycling stability of the adsorbent was improved.

Comparative secretome metabolic dysregulation by six engineered dietary nanoparticles (EDNs) on the simulated gut microbiota.

The potential use of engineered dietary nanoparticles (EDNs) in diet has been increasing and poses a risk of exposure. The effect of EDNs on gut bacterial metabolism remains largely unknown. In this study, liquid chromatography-mass spectrometry (LC-MS) based metabolomics was used to reveal significantly altered metabolites and metabolic pathways in the secretome of simulated gut microbiome exposed to six different types of EDNs (Chitosan, cellulose nanocrystals (CNC), cellulose nanofibrils (CNF) and polylactic-co-glycolic acid (PLGA); two inorganic EDNs including TiO2 and SiO2) at two dietary doses. We demonstrated that all six EDNs can alter the composition in the secretome with distinct patterns. Chitosan, followed by PLGA and SiO2, has shown the highest potency in inducing the secretome change with major pathways in tryptophan and indole metabolism, bile acid metabolism, tyrosine and phenol metabolism. Metabolomic alterations with clear dose response were observed in most EDNs. Overall, phenylalanine has been shown as the most sensitive metabolites, followed by bile acids such as chenodeoxycholic acid and cholic acid. Those metabolites might be served as the representative metabolites for the EDNs-gut bacteria interaction. Collectively, our studies have demonstrated the sensitivity and feasibility of using metabolomic signatures to understand and predict EDNs-gut microbiome interaction.

Safety observation study on haemophilus influenza type B conjugate vaccines injected at different sites in Chinese infants.

In the present study, the safety of Haemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.

Associations of per- and polyfluoroalkyl substances and alternatives with reproductive hormones in women of childbearing age.

BACKGROUND: Experimental studies suggested that per- and polyfluoroalkyl substances (PFAS) may have endocrine-disrupting effects. However, the epidemiological evidence on the associations of PFAS with female reproductive hormones is sparse and limited to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). OBJECTIVE: To evaluate effects of legacy and emerging PFAS alternatives on female reproductive hormones. METHODS: A total of 433 reproductive-aged females were recruited from 2014 to 2016. Information on age, age at menarche, gravity, menstrual cycle, BMI, education, and income was obtained from medical records and questionnaires. Serum samples were collected for reproductive hormones, and plasma samples for PFAS measurement by ultraperformance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Multiple linear regression and quantile g-computation (q-gcomp) were used to examine the associations of individual PFAS and their mixture with reproductive hormones. RESULTS: Multiple linear regression analysis showed significant effects of certain PFAS on total testosterone (TT): adjusted estimate (ß) for perfluoroheptanoic acid (PFHpA) was 0.57 (95% CI: 0.18, 0.97). Moreover, a positive association was detected between PFAS mixture and TT in the q-gcomp model. Higher concentrations of 6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) were associated with significantly lower prolactin level (ß = -0.07, 95% CI: -0.14, -0.001). CONCLUSION: Our study found that exposure to PFAS alternatives was associated with altered levels of reproductive hormones in women of childbearing age.

Cellular FLICE-inhibitory protein protects against cardiac remodelling after myocardial infarction.

Cellular FLICE-inhibitory protein (cFLIP) is a member of the tumour necrosis factor signalling pathway and a regulator of apoptosis, and it has a role in cardiac remodelling following myocardial infarction (MI) that remains largely uncharacterised. This study aimed to determine the function of cFLIP as a potential mediator of post-infarction cardiac remodelling. Our results show diminished cFLIP expression in failing human and murine post-infarction hearts. Genetically engineered cFLIP heterozygous (cFLIP+/-, HET) mice, cardiac-specific cFLIP-overexpressing transgenic (TG) mice and their respective wild-type (WT) and non-transgenic controls were subjected to MI by permanent ligation of their left anterior descending artery. Cardiac structure and function were assessed by echocardiography and pressure-volume loop analysis. Apoptosis, inflammation, angiogenesis, and fibrosis were evaluated in the myocardium. The HET mice showed exacerbated left ventricular (LV) contractile dysfunction, dilatation, and remodelling compared with WT mice 28 days after MI. Impaired LV function in the HET mice was associated with increases in infarct size, hypertrophy, apoptosis, inflammation, and interstitial fibrosis, and reduced capillary density. The TG mice displayed the opposite phenotype after MI. Moreover, adenovirus-mediated overexpression of cFLIP decreased LV dilatation and improved LV function and remodelling in both HET and WT mice. Further analysis of signalling events suggests that cFLIP promotes cardioprotection by interrupting JNK1/2 signalling and augmenting Akt signalling. In conclusion, our results indicate that cFLIP protects against the development of post-infarction cardiac remodelling. Thus, cFLIP gene delivery shows promise as a clinically powerful and novel therapeutic strategy for the treatment of heart failure after MI.

Emerging and legacy PFAS and cytokine homeostasis in women of childbearing age.

Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals. Legacy PFAS have been phased out of production in most developed countries and emerging PFAS (short-chain PFAS and polyfluorinated compounds) are used as legacy PFAS alternatives. The effect of legacy and emerging PFAS on cytokine homeostasis in human remains poorly understood. This study aimed to evaluate the associations between legacy and emerging PFAS and cytokine profiles, and identify the main contributors to the disturbance of cytokine homeostasis. We quantified 21 PFAS in 198 Chinese women of childbearing age from 2015 to 2016. 13 cytokines were measured using the Meso Scale Discovery U-PLEX and V-PLEX platforms. The associations between PFAS exposure and cytokine levels were assessed using multiple linear regression (single-exposure), and Bayesian kernel machine regression (BKMR) models (PFAS mixture exposure). In single PFAS models, legacy and alternative PFAS were positively associated with Th1 and Treg cytokines, and negatively associated with Th2 and Th17 cytokines. For instance, each ln-unit increase in 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) was associated with a decrease in IL-10 by - 0.228 (95% CI: - 0.336, - 0.120), - 0.153 (95% CI: - 0.277, - 0.030), and - 0.174 (95% CI: - 0.339, - 0.010), respectively. The BKMR model showed a significantly positive association of PFAS mixture with TGF-ß and a negative association with IL-10. Overall, these results indicate that both legacy and emerging PFAS may affect the homeostasis of cytokines.

Environmental exposure to per- and polyfluoroalkyl substances and sleep disturbance in pregnant women: A prospective cohort study.

Previous studies on the association between exposure to per- and polyfluoroalkyl substances (PFAS) and sleep patterns in pregnant women are limited. This cohort study aims to assess the associations between PFAS and sleep quality in pregnant women. Of the 4127 women who participated in the Shanghai Birth Cohort, 3174, 3070, and 2887 women in their first, second, and third trimesters of gestation, respectively, were included in our analysis. Sleep measures were taken using the Pittsburgh Sleep Quality Index questionnaire. Ten PFAS were measured in blood samples collected in early pregnancy. We first evaluate the associations between individual PFAS and sleep quality in the three trimesters. Weighted quantile sum (WQS) regression models were performed to test the overall effect of the PFAS mixture on sleep quality during the three trimesters. Longitudinal analyses throughout pregnancy were performed with generalized estimating equation models. Furthermore, the effect of the PFAS mixture on longitudinal sleep patterns was examined using longitudinal latent class analyses combined with WQS models. The single pollutant analysis suggested that most PFAS were associated with increased sleep disturbance risk, lower sleep efficiency, and shorter sleep duration in the three trimesters. Similarly, the WQS models revealed a significant association between the PFAS mixtures and elevated sleep disturbance risk in pregnant women, with perfluorobutane sulfonate acting as the predominant risk factor. Additionally, the longitudinal analysis confirmed the effects of PFAS exposure on increased sleep disturbance over time. The PFAS mixture was positively associated with higher risks of poor sleep quality and sleep medicine use [adjusted odds ratio (aOR) = 1.10; 95 % confidence interval (95%CI): 1.01, 1.20; and aOR = 1.25 (95%CI: 1.04, 1.50) respectively] throughout the three trimesters. Our study suggests that PFAS may increase the risk of sleep disturbance in pregnant women. Further studies are needed to confirm our results and elucidate potential mechanisms.

Environmental antibiotics exposure in school-age children in Shanghai and health risk assessment: A population-based representative investigation.

BACKGROUND: The widespread use of antibiotics has left extensive residues in the environment and food. Antibiotics can accumulate in human body. As the potential health risks of antibiotic exposure in children are of a great concern in recent years, our study aimed to describe the status of antibiotic exposure in primary school students in Shanghai, China, and to explore the relationships of dietary patterns with internal antibiotic levels. METHODS: The Shanghai Children's Health, Education, and Lifestyle Evaluation (SCHEDULE) Survey was a cross-sectional study with a staged, cluster random sample of all primary school students in Shanghai, China. In the present study, we randomly selected 2199 children aged 6-12 years old. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression models were used to investigate dietary patterns associated with detection rates of antibiotics. RESULTS: The detection rates of individual antibiotics ranged from 4.3% to 30.7%. 68.7% of children were exposed to at least one antibiotic. There was a significant difference in child exposure to overall antibiotics by residential locations (60.9% in urban vs. 71.1% in suburban areas). Principal component analyses suggested that higher unhealthy dietary pattern scores were significantly associated with increased detection rates of tetracyclines [1.27 (95% CI: 1.18, 1.38)] and sulfonamides [1.20 (95% CI: 1.05, 1.36)]. In addition, 9.05% of children had a hazard index (HI) value greater than 1, which was mainly contributed by ciprofloxacin. CONCLUSIONS: School-age children were widely exposed to antibiotics in Shanghai. Unhealthy diet was associated with a higher level of antibiotic exposure.

Preconception exposure to perfluoroalkyl and polyfluoroalkyl substances and couple fecundity: A couple-based exploration.

Numerous studies have examined the adverse health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) but it remains unclear whether preconception exposure to PFAS affects couple fecundity. This prospective preconception cohort study with 936 Chinese couples aimed to comprehensively assess the effects of PFAS on couple fecundity [measured by the time to pregnancy (TTP)] and infertility (i.e., TTP > 12 menstrual cycles) with a focus on the effects of partner-specific exposure and joint-effects of couple-based exposure. Twenty-five PFAS were quantified in plasma from each partner, including seven branched isomers, two chlorinated polyfluoroalkyl ether sulfonic acids, four emerging PFAS replacements [i.e., 6:2 fluorotelomer phosphate diester (6:2 diPAP) and three short-chain alternatives: perfluoro-n-butanoicacid, perfluorobutane sulfonate and perfluoroheptanoic acid (PFHpA)]. Using a two-phase regression approach composed of elastic net regression and principal component analysis, we found that exposure to 6:2 diPAP and PFHpA rather than legacy PFAS in women and the couple-based exposure patterns characterized by high level of female 6:2 diPAP were significantly associated with reduced couple fecundity, which was independent of the adjustment of co-exposed PFAS homogenous from both partners. For example, a ln unit increase in female 6:2 diPAP was associated with 15 % [fecundity odds ratio (FOR) = 0.85, 95 %CI: 0.76, 0.96)] lower odds of couple fecundability (i.e., longer TTP) and 45 % increased risk of infertility [OR = 1.45 (95 %CI: 1.16, 1.81)], respectively. While most PFAS in men were not associated with couple fecundity, certain PFAS (e.g., perfluorohexane sulfonic acid) in men were negatively associated with infertility risk. However, the combined effects of PFAS mixture in couples were nonsignificant. Our findings suggest that PFAS in men and women may exert different impacts on couple fecundity. Preconception exposure to 6:2 diPAP and PFHpA in women may have the potential to impair couple fecundity.